The goal of the proposed project is to gain quantitative information concerning the role of intercellular contact in modifying the response of malignant and non-malignant cells exposed to ionizing radiation in vitro. Using the endpoint of colony formation, cell survival after acute exposure will be studied for a number of cell types growing singly or under conditions simulating in vivo intercellular contact, to determine whether a modified Dq can be predicted under the latter growth conditions. Since such a modification of Dq is generally interpreted as a modification of cellular ability to withstand and/or repair sublethal damage, the kinetics and degree of completion of repair of such damage will be examined by dose fractionation techniques. In addition, "repair" of damage as assayed by cell viability will be characterized and compared for cells remaining in contact for long periods after exposure, as opposed to cells that grow as individuals after irradiation. Combined treatment of single cells or cell clusters with radiation and drugs known to have specific metabolic or radiochemical mechanisms may provide some insight into the mechanism(s) by which cell survival is altered. Finally, the effect of the two growth conditions on the radiosensitivity and repair of DNA single strand breaks, as measured on alkaline sucrose gradients, will be determined and compared to cellular survival. By these experiments, we hope to characterize the conditions under which intercellular contact leads to a modification of cellular survival, and perhaps to elucidate some of the molecular or biochemical mechanisms involved.